Cancer cells can dodge chemotherapy by entering a state that bears similarity to certain kinds of senescence, a type of “active hibernation” that enables them to weather the stress induced by aggressive treatments aimed at destroying them, a new study suggests. The findings, published in the journal Cancer Discovery, indicated that this biological process could help explain why cancers so often recur after treatment.
“Acute myeloid leukemia can be put into remission with chemotherapy, but it almost always comes back, and when it does it’s incurable,” said senior author Ari M. Melnick from Weill Cornell Medicine.
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The research was done in both organoids and mouse models made from patients’ samples of acute myeloid leukemia (AML) tumors. In the study, the researchers found that when AML cells were exposed to chemotherapy, a subset of the cells went into a state of hibernation, or senescence, while at the same time assuming a condition that looked very much like inflammation.
They looked similar to cells that have undergone an injury and need to promote wound healing — shutting down the majority of their functions while recruiting immune cells to nurse them back to health. Further research revealed that this inflammatory senescent state was induced by a protein called ATR, suggesting that blocking ATR could be a way to prevent cancer cells from adopting this condition.
The investigators tested this hypothesis in the lab and confirmed that giving leukemia cells an ATR inhibitor before chemotherapy prevented them from entering senescence, thereby allowing chemotherapy to kill all of the cells. (IANS/SP)